Magainins environments

The amphipathic a-helical class of host defense peptides is the most abundant and most well-characterized class. Upon interaction with the hydrophobic membrane environment, the largely unstructured peptide adopts an amphipathic ct-helical conformation with one helical face containing the majority of the hydrophobic residues, the opposite containing a large proportion of the polar residues. These peptides are often short (<40 amino acids), devoid of cysteine residues, and found to be unstructured or linear in nonhydrophobic environments. Peptides found within this class include the antimicrobial peptide alamethicin, bee venom melittin, the magainins, and the human cathelicidin LL-37. ... 

Orientational constraints have been collected for a wide variety of molecular systems from synthetic polymers [32, 33] to structural proteins, such as silk [34, 35]. Orientational constraints have also been collected for retinal bound to bacteriorhodopsin [36], suggesting a host of ligand receptor systems that might be studied. Orientational constraints have been collected on other synthetic and biosynthetic polypeptides in bilayer environments, such as Magainin-2, a toxin from frog skin [37], the M2 8 from the acetylcholine receptor [38] and M2-TMP from Influenza A virus [39]. Such studies have led to a description of the orientation of a-helices relative to the bilayer. Proteins such as the fd and Pfl bacteriophage coat proteins have also been... 

The second major structural class studied is the O-helical class. Interestingly, such structures tend to be rather disorganized in aqueous solution, but they become a-helical structured upon entering a membrane environment or exposure to nonpolar solvents (89,90). The predominant structures observed upon interaction with membranes are helix-bend-helix with a 9-16 amino acid amphipathic a-helix, a 2-4 residue bend, and a 11-14 amino acid amphipathic but more hydrophobic a-helix, as demonstrated by two-dimensional NMR of cecropins A and B, melittin, the magainins, and a synthetic cecropin-melittin hybrid (89,91-93). A small variation is provided by mammalian cecropin Pi, which comprises an uninterrupted amphiphilic helix for 24 amino acids, bounded by 2-4 residues at the N- and C-termini. 

A number of design principles are not specific to magainin-related peptides, but are shared with many peptides, or domains of proteins, which disrupt membrane function. Common features of working models include an abundance of basic amino acids to provide an electrostatic attraction to negatively-charged membranes the adoption of an alpha-helical structure in hydrophobic environments and the assembly of peptide monomers into a multimeric structure that can span a membrane and form a hydrophilic pore (e.g. 13-16),... 

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